The central nervous system is known to play an important role in energy homeostasis through its control of behavioral, hormonal, and metabolic events. However, major questions about the role of the central nervous system in obesity remain unanswered. These questions include the identity and organization of the specific neural populations that comprise the regulatory systems and the nature of the effector mechanisms by which events in the central nervous system ultimately affect adipose tissue. The proposed experiments use behavioral, biochemical and anatomical techniques to test hypotheses about the role of central monoamines and in particular, norepinephrine, in energy homeostasis. Experiments are proposed to be conducted in genetically obese mice in which abnormalities have been uncovered in catecholaminergic systems. The relationship of spontaneously occurring obesity to monoamine function will be studied. In the diabetes (db/db) mouse, reduction of central catecholamine levels improves the diabetes syndrome by decreasing body weight, food intake, body fat and blood glucose, increasing pancreatic islet granulation and maintaining insulin production. Experiments will be undertaken to test specific hypotheses about how these effects are mediated. Data are accumulating in several animal models of obesity including some genetic obesities that altered autonomic nervous system function contributes to abnormal energy homeostasis. Experiments are proposed to continue an examination of the function of the autonomic nervous system in genetically obese mice and to examine the role of the central catecholamine systems in the control of autonomic function.